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Kainate receptor modulation by NETO2

机译：Neto2的Kinate受体调节

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摘要

Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse(1-7). In the brain, the trafficking, gating kinetics and pharmacology of kainate receptors are tightly regulated by neuropilin and tolloid-like (NETO) proteins(8-11). Here we report cryo-electron microscopy structures of homotetrameric GluK2 in complex with NETO2 at inhibited and desensitized states, illustrating variable stoichiometry of GluK2-NETO2 complexes, with one or two NETO2 subunits associating with GluK2. We find that NETO2 accesses only two broad faces of kainate receptors, intermolecularly crosslinking the lower lobe of ATD(A/C), the upper lobe of LBDB/D and the lower lobe of LBDA/C, illustrating how NETO2 regulates receptor-gating kinetics. The transmembrane helix of NETO2 is positioned proximal to the selectivity filter and competes with the amphiphilic H1 helix after M4 for interaction with an intracellular cap domain formed by the M1-M2 linkers of the receptor, revealing how rectification is regulated by NETO2.
机译：谷氨酸门控Kinate受体在脊椎动物的中枢神经系统中普遍存在，介导在后期的突触传递，并调节预先生的发射器释放（1-7）。在大脑中，Kinate受体的贩运，门控动力学和药理学受到神经素素和诸如Tolloid样（Neto）蛋白（8-11）的紧密调节。在这里，我们在抑制和脱敏的状态下将Homotetramic Gluk2的低温电子显微镜结构报告了同种聚特异性Gluk2的络合物，示出了Gluk2-NetO2配合物的可变化学计量，其中一个或两个NetO2亚基与Gluk2相关联。我们发现NetO2只能仅接受kinate受体的两个宽面，分离间交联ATD（A / c）的下叶，LBDB / D的上叶和LBDA / c的下叶，说明了NetO2如何调节受体浇注动力学。 NetO2的跨膜螺旋定位于选择性过滤器的近端，并与由受体的M1-M2接头形成的细胞内帽结构域相互作用，与受体形成的细胞内帽结构域相互竞争，揭示了如何通过NetO 2调节整流。

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  • 来源
    《Nature》 |2021年第7884期|325-329|共5页
  • 作者

    He Lingli; Sun Jiahui; Gao Yiwei; Li Bin; Wang Yuhang; Dong Yanli; An Weidong; Li Hang; Yang Bei; Ge Yuhan; Zhang Xuejun Cai; Shi Yun Stone; Zhao Yan;

  • 作者单位

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Chinese Acad Sci Inst Biophys State Key Lab Brain & Cognit Sci Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Nanjing Univ Sch Med Model Anim Res Ctr Minist Educ Key Lab Model Anim Dis Study Nanjing Peoples R China|Nanjing Univ Affiliated Drum Tower Hosp Dept Neurol State Key Lab Pharmaceut Biotechnol Med Sch Nanjing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Chinese Acad Sci Inst Biophys State Key Lab Brain & Cognit Sci Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Chinese Acad Sci Inst Biophys State Key Lab Brain & Cognit Sci Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Nanjing Univ Sch Med Model Anim Res Ctr Minist Educ Key Lab Model Anim Dis Study Nanjing Peoples R China|Nanjing Univ Affiliated Drum Tower Hosp Dept Neurol State Key Lab Pharmaceut Biotechnol Med Sch Nanjing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

    Nanjing Univ Sch Med Model Anim Res Ctr Minist Educ Key Lab Model Anim Dis Study Nanjing Peoples R China|Nanjing Univ Affiliated Drum Tower Hosp Dept Neurol State Key Lab Pharmaceut Biotechnol Med Sch Nanjing Peoples R China|Nanjing Univ Inst Brain Sci Nanjing Peoples R China|Nanjing Univ Chem & Biomed Innovat Ctr Nanjing Peoples R China;

    Chinese Acad Sci Inst Biophys CAS Ctr Excellence Biomacromol Natl Lab Biomacromol Beijing Peoples R China|Chinese Acad Sci Inst Biophys State Key Lab Brain & Cognit Sci Beijing Peoples R China|Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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